The goal of this proposal is to create a hand-held active instrument for manual micromanipulation that provides compensation of physiological hand tremor and other unintended motion by generating an equal but opposite deflection of its own tip. This deflection will effectively subtract the erroneous motion from the overall instrument motion, enabling positioning accuracy of 10 um or better, and allowing direct manual micromanipulation to supplant automated micromanipulation in many tasks. Filtering algorithms for both tremor and low-frequency drift will be implemented in the instrument. The device will be used both for microinjection and micromanipulation in the cell biology laboratory, and for clinical microsurgery, especially in vitreoretinal procedures. This work will, therefore, have both basic and clinical application, contributing to advances in both biomedical research and human health. In addition to design and construction of the instrument with the necessary sensors, actuators and control system, the research will involve development of a testbed for initial repeatable experimentation with the instrument, including an external tip position measurement apparatus for independent verification of performance. This apparatus will enable, for the first time, three-dimensional, micron-accurate recordings of human manual micromanipulation, and will be used also to record raw hand motion data to be used as input for the initial experiments. In the initial tests, the instrument will be mounted on a high-precision robotic wrist, which will be subjected to recorded movements containing both desired and undesired components. Each test will be run once with and once without active compensation, and quantitative results will be compared. After these robotic demonstrations of the instrument's performance, human subject trials will be conducted in both the cell biology laboratory and the surgical practice suite. The performance of the instrument will again be evaluated using quantitative results from these experiments.